Is AKAP1 p.Ala692Val (c.2075C>T) pathogenic?

AKAP1 p.Ala692Val (c.2075C>T) is classified Uncertain significance in AKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.1298); Absent from gnomAD v4.1.

How common is AKAP1 p.Ala692Val (c.2075C>T) in the general population?

AKAP1 p.Ala692Val (c.2075C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AKAP1 p.Ala692Val (c.2075C>T)?

AlphaMissense predicts likely benign (score 0.1298) — an in-silico prediction, not a clinical call.

AKAP1 p.Ala692Val

c.2075C>T · VCV4261398

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1298 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1298	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	donor gain · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 5.3e-08 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AKAP1
Protein: p.Ala692Val
Coding: c.2075C>T
MANE Select: NM_003488
Type: single nucleotide variant
Location: chr17:57112590 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.67 (gnomAD)
Structure: AlphaFold pLDDT 57.02

Full AKAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AKAP1 c.1976-6A>G Benign ★★ same type
AKAP1 p.Ala218Thr Benign ★★ same type
AKAP1 p.Gly323Ser Benign ★★ same type
AKAP1 p.Pro475= Benign ★★ same type
AKAP1 p.Pro818= Benign ★★ same type
AKAP1 p.Ser330Gly Benign ★★ same type
AKAP1 p.Ser388= Benign ★★ same type
AKAP1 p.Thr521Ile Likely benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/akap1-p-ala692val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown